Goal-directed behavior requires the ability to monitor and execute internal goals and intentions, maintain and manipulate information in working memory, select task-relevant information, and organize action plans to accomplish these goals. The proposed research program will employ a multidisciplinary approach directed toward investigations of the neural mechanisms underlying such "executive control" processes. Neurocognitive methods-particularly neuroimaging and neuropsychological techniques- have sharpened our understanding of such processes. Indeed, it is well established that the prefrontal cortex (PFC) is critically involved in the executive control of a variety of goal-directed behaviors. Yet, our understanding of how the PFC is itself organized and how it dynamically controls other cortical and subcortical regions is less well understood. We will develop and utilize a wide range of complementary methodologies to explore executive control processes. These methods include physiological techniques (e.g. single unit recording in monkeys, functional MRI in healthy subjects, electocorticography in epilepsy patients), neuropsychological methods (e.g. behavioral studies of patients with focal lesions due to stroke, transcranial magnetic stimulation of healthy subjects), pharmacological techniques (e.g. effects of dopaminergic agents in healthy subjects, behavioral studies of Parkinson's disease patients on and off their medication) and developmental methods (e.g., studies of healthy children). The Core of the Program Project will provide detailed neuropsychological and neuroanatomical assessment of neurological patients, state-of-the-art neuroimaging and electrophysiological facilities, and an integrative intellectual environment that will facilitate cross-fertilization of ideas and methods among investigators. Three proposed projects will address issues of executive control processes associated with goal-directed behavior. Project 1 will address the functional organization of regions within PFC and how they contribute to executive control. Project 2 will focus on mechanisms by which the PFC initiates top-down signals to posterior cortical regions in order execute control over bottom-up activations. Project 3 will focus 'on fronto-striatal circuits and how they contribute to decision-making and response plans. The knowledge gained from this work has the potential to be of central clinical significance, as many neurological disorders include impairment in executive control processes. Moreover, such knowledge may provide a foundation for developing cognitive and pharmacological therapies for treating the wide range of disorders characterized as deficits in executive control.